肢体与心肌缺血后处理对兔急性心肌缺血再灌注损伤的对比研究

目的探讨在体状态下,肢体缺血后处理是否具有减轻心肌缺血再灌注损伤的作用,并探讨其机制。方法在新西兰大白兔心肌缺血再灌注模型,给予冠状动脉左前降支(LAD)30 m in缺血,180 m in再灌注。所有动物随机分为4组(每组10只):(1)对照组;(2)心肌缺血预处理组;(3)心肌缺血后处理组;(4)肢体缺血后处理组;在缺血前、后及再灌注结束后分别测定血浆磷酸肌酸激酶(CK)和丙二醛(MDA)活性;实验结束后,测定心肌梗死面积并检测心肌组织髓过氧化物酶(MPO)活性。结果心肌缺血预处理组、心肌缺血后处理组和肢体缺血后处理组心肌梗死面积分别为15.5%±1.7%、16.2%±2.0%、17.1%±1.7%,均明显低于对照组(31.5%±1.3%,P<0.01);再灌注3h末血浆CK活性,肢体缺血后处理组与对照组分别为18.0 IU/g±1.6 IU/g与45.6 IU/g±5.5IU/g(P<0.01);缺血预处理组、缺血后处理组和肢体缺血后处理组在再灌注3h末MDA活性分别为2.12μmol/m l±0.30μmol/m l、2.17μmol/m l±0.24μmol/m l和2.16μmol/m l±0.33μmol/m l,均明显低于对照组(3.49μmol/m l±0.32μmol/m l(P<0.01);心肌缺血预处理组、心肌缺血后处理组和肢体缺血后处理组中性粒细胞在缺血心肌的聚集程度,即组织MPO活性分别为1.43 U/100 g±0.32U/100 g、2.26 U/100 g±0.28 U/100 g和2.45 U/100 g±0.28 U/100 g,均较对照组(5.44 U/100 g±0.46 U/100 g)明显降低(P<0.01)。结论对于已经缺血的心肌,在再灌注前给予肢体短暂缺血再灌注处理具有与心肌缺血预处理相似的心肌保护作用。这种远隔器官缺血后处理心肌保护作用可能与减轻活性氧的损伤及抗氧化作用加强有关。

Correlation of limb and myocardial ischemia postconditioning with acute myocardial reperfusion injury

OBJECTIVE: We tested the hypothesis that remote postconditioning, which is induced by a single 5-min episode of femoral artery occlusion and reperfusion applied just before the onset of coronary artery reperfusion, protects the myocardium from reperfusion injury. METHODS: In anesthetized open-chest rabbits, the left anterior descending artery (LAD) was occluded for 30 min and reperfused for 3 hrs. All rabbits were randomly divided into four groups (n = 10 in each group): (1) Control: LAD occlusion and reperfusion only, with no other intervention; (2) Myocardial ischemic preconditioning (Pre-con): Three cycles of myocardial ischemia (5 min) and reperfusion (5 min) preceded the index ischemia/reperfusion protocol; (3) Myocardial ischemic postconditionng (Post-con): After 30 min of LAD occlusion, reperfusion was initiated for 30 s followed by 30 s reocclusion. Three cycles of myocardial ischemia (30 s) and reperfusion (30 s) followed the index ischemia/reperfusion protocol. (4) Remote postconditioning (Re Post-con): After 24 min of LAD occlusion, the femoral artery was occluded for 5 min and released for 1 min before 3 hrs of LAD reperfusion. Myocardial infarct size and tissue myeloperoxidase (MPO) activity were determined at the end of the experiment. Plasma creatine kinase (CK) activity and malondialdehyde (MDA) activity were measured at baseline, the end of ischemia, and after 3 hrs of reperfusion respectively. RESULTS: Myocardial infarct size was significantly reduced in Pre-con (15.5% +/- 1.7%, P < 0.01), Post-con (16.15% +/- 2.05%, P < 0.01) and Re Post-con (17.11% +/- 1.70%, P < 0.01) groups as compared to Control (31.46% +/- 1.28%). Results were confirmed by plasma CK activity (in Re Post-con 18.0 IU/g +/- 1.6 IU/g vs. Control 45.6 IU/g +/- 5.5 IU/g). Plasma MDA was significantly less at 3 hrs of reperfusion in Pre-con (2.12 micromol/ml +/- 0.30 micromol/ml, P < 0.01), Post-con (2.17 micromol/ml +/- 0.24 micromol/ml, P < 0.01) and Re Post-con (2.16 micromol/ml +/- 0.33 micromol/ml, P < 0.01) than that in Control (3.49 micromol/ml +/- 0.32 micromol/ml). Neutrophil accumulation (MPO activity) in the area at risk was less in Pre-con (1.43 U/100 g +/- 0.32 U/100 g, P < 0.01), Post-con (2.26 U/100 g +/- 0.28 U/100 g, P < 0.01) and Re Post-con (2.45 U/100 g +/- 0.28 U/100 g, P < 0.01) than that in Control (5.44 U/100 g +/- 0.46 U/100 g). CONCLUSION: Remote limb postconditioing applied just before the onset of coronary artery reperfusion provides potent myocardial infarct size reduction, which is similar to the cardioprotective effect of myocardial postconditioning exerted during the first minutes of coronary reperfusion. The potential mechanism of this inter-organ remote postconditioning phenomenon might be associated with decreasing the injury caused by oxygen free radicals and strengthening the action of antioxidation.